Project Summary Retinal rod and cone photoreceptor cells mediate the essential first steps in vision by signaling light intensity and its modulation. Although the initial biochemical steps that transduce light into electrical signals in the outer segments of photoreceptors are well understood, much less is known about how outer segment currents are transformed by voltage-sensitive conductances and influenced by adaptation and circadian regulation in vivo. The work proposed in this application will investigate photoreceptor physiology the living eye and the mechanisms by which photoreceptor physiology is modulated to influence visual sensitivity and kinetics, and to mitigate photoreceptor stress. Using primarily a combination of ex vivo and in vivo electrophysiological approaches, three aims will be investigated: 1. Determine the role of Kv2.1 channels in rods. 2. Define the mechanisms that constrain photoreceptor sensitivity and kinetics in vivo. 3. Determine how photoreceptor properties are modulated by the circadian clock.